The land area which is now within the town limits of Clifton was sparsely settled farm land by the late 1700s, with 1,200 acres of Popes Head Creek belonging to William E. Beckwith. Several events affected the area just prior to 1865. First, the section of the Orange and Alexandria Railroad between Alexandria and Manassas was completed in 1852, traversing William Beckwith's land. Secondly, between 1861 and 1865 this rail line was used strategically for transporting supplies and troops for the Union Army which incorporated it into the U. S. Military Railroad System. At what is now Clifton, the Union Army in 1863 built Devereux Station, a siding used for loading firewood onto the engines. Also in 1863, William Beckwith died, leaving no heirs and about 1,000 acres north of the Orange and Alexandria tracks in his estate to be sold and smaller parcels south of the tracks to be distributed to his freed slaves.

Following the Civil War, many former soldiers and others from the North migrated into Fairfax County. Harrison G. Otis followed this pattern and moved to the county from Ontario County, New York. In 1868 at the age of 54, he purchased land parcels along the railroad line from the Beckwith estate. In this same year the depot's name was changed to Clifton Station. Within a year, Clifton had become a United States post office, with Otis as the postmaster. He continued his vigorous development pursuits: purchasing land, undertaking vineyard cultivation, and opening roads which gave access to the railroad from points north, south, and west of Clifton. He also built the Clifton Hotel next to the tracks as a residential and tourist hotel, and by 1870 had further expanded his activities to include saw milling. The U. S. Census records for the Centreville District of Fairfax County indicate that in 1880 Otis' brother, W. B. Otis and his wife, Anna Elizabeth, and Otis' sister, Clara, were all residents of the area.

Over the next ten years Clifton developed the amenities needed to support a settlement of twenty families, according to the 1878 Hopkins Map. The town featured four churches, a school, saw and grist mills, four general merchants, a blacksmith shop, and wagon shops. The Hetzel House (1870), the Mayhugh Tavern (circa 18701 and the Quigg House (1876) were all standing by this time. The early churches which still survive are the Clifton Presbyterian Church (1870) and the Clifton Baptist Church (1877, building replaced in 1912).

By the early 1880s Clifton was able to take advantage of its short distance from Washington, D. C. by rail. In the Virginia Midland Railway Excursion Guide, published in 1882 by the successor to the Orange and Alexandria Railroad, Clifton House (Otis' Clifton Hotel) was listed as a resort. This role for Clifton was primarily attributable to the summer residents, many from Washington, who were attracted to the country village.